The topical application to the gingiva of beagle dogs of minute amounts of human plaque extracts and bacterial endotoxins (a model which simulates periodontal disease) has demonstrated a variation in the acute gingival inflammation-inducing potential of these substances and the release of endogenous mediators. This three-phased proposal is designed to fractionate plaque into specific components and study their inflammatory potential in vivo. Phase I is designed to obtain specific plaque fractions from saline plaque extracts using molecular sieve chromatography and to characterize each fraction chemically and biologically. The inflammation-inducing potential of each fraction will be evaluated on the basis of crevicular fluid collected and levels of endogenous mediators (kallicrein, kinin, histamine, prostaglandins) measured therein. Inhibition studies of active fractions will be performed in Phase II to delineate the initiating and mediating mechanisms. Initially, fractions will be treated with inhibitors such as proteases to specifically abolish certain components, prior to in vivo testing. In another series, the animals will be treated systemically with inhibitors of immune mechanisms such as cobra venom factor prior to application of fractions, to determine initiating mechanisms. Ina third series, the animals will be pretreated with endogenous mediator antagonists to determine the role of these mediators in the response. The inflammatory parameters measured will be compared to those in the untreated systems. Active fractions will be further purified and analyzed during Phase III. The data obtained in these studies will result in a better understanding of the mechanisms involved in periodontal disease. More effective means of prophylaxis and therapy can thus be established.